MECHANISMS OF ADAPTATION AND EXCITATION

适应和兴奋机制

• 批准号: 6342582
• 负责人: JOHN E LISMAN
• 金额: $ 26.37万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-06-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6342582
• 关键词: 2'3' cyclic nucleotide phosphodiesterase; alternatives to animals in research; calcium; calmodulin dependent protein kinase; cone cell; electrophysiology; fresh water environment; horseshoe crabs; light adaptations; membrane channels; microelectrodes; retinal adaptation; rod cell; visual photoreceptor; visual photosensitivity; visual phototransduction

DESCRIPTION (Adapted from applicant's abstract): This proposal would continue a long-term investigation of phototransduction mechanisms in Limulus photoreceptors. CaM-kinase has been implicated in the light-dependent phosphorylation of arrestin, but its function is unknown. The possible role of CaM-kinase in regulating equivalent light and other transduction processes will be tested by intracellular injection of active kinase or kinase inhibitors. A second set of experiments will attempt to elucidate the late stages of transduction which remain unknown. These experiments are predicated on the hypothesis that the Ca2+ elevation produced by the phospholipase C (PLC)-IP3 pathway triggers a cyclase; the resulting elevation of cyclic nucleotide could activate the cyclic nucleotide-gated channels observed in earlier experiments on excised patches. If confirmed, this hypothesis would provide a complete pathway from rhodopsin to channel and a framework for understanding the degeneration produced by light in invertebrates. A final set of experiments builds upon the earlier observation that CaM may also be involved in an early step of transduction. Physiological and biochemical experiments are proposed to localize this step. Preliminary evidence suggests that it may be at PLC. These results, if confirmed, may reveal altogether new regulatory mechanisms for phospholipase and Ca2+, insight that may be important in understanding the role of this enzyme in vertebrate cones, where its role remains completely unclear.

描述（改编自申请人摘要）：本提案将 继续长期研究光传导机制， 鲎光感受器。 钙调素激酶与 抑制蛋白的光依赖性磷酸化，但其功能尚不清楚。 钙调素激酶在调节等效光和其他方面的可能作用 转导过程将通过细胞内注射活性 激酶或激酶抑制剂。 第二组实验将试图 阐明仍然未知的转导的晚期阶段。 这些 实验是基于这样的假设，即Ca 2+升高 由磷脂酶C（PLC）-IP 3途径产生的磷脂酶C（PLC）-IP 3途径触发环化酶; 环核苷酸的升高可以激活环 在早期的实验中观察到的核苷酸门控通道切除 补丁. 如果得到证实，这一假设将提供一个完整的途径， 从视紫红质到通道，以及理解变性的框架 无脊椎动物体内由光线产生的 最后一组实验建立在 早期的观察，钙调素也可能参与早期步骤， 转导 生理和生化实验建议， 将此步骤本地化。 初步证据表明，它可能在PLC。 这些结果如果得到证实，可能会揭示全新的调控机制 对于磷脂酶和Ca 2+，了解可能是重要的， 这种酶在脊椎动物视锥细胞中的作用 完全不清楚